When a human cell is faced with the task of replicating six billion letters of DNA each time it divides, it doesn’t read each chromosome in one slow pass. Instead, its DNA replication machinery divides up the task by beginning work at many origin points. Some segments get copied earlier, some later.
Geneticists at HMS and the Broad Institute of Harvard and MIT have found that this replication plan—including the locations of the origin points and the order in which DNA segments get copied—varies from person to person.
Their study, published in the November 20, 2014, issue of Cell, also identifies the first genetic variants that orchestrate replication timing.
“Everyone’s cells have a plan for copying the genome. The idea that we don’t all have the same plan is surprising and interesting,” says Steven McCarroll, an HMS assistant professor of genetics, director of genetics for the Broad’s Stanley Center for Psychiatric Research, and senior author of the paper.
“It’s a new form of variation that no one had expected,” says first author Amnon Koren, postdoctoral fellow at HMS and the Broad.
DNA replication is one of the most fundamental cellular processes. Any variation among people is likely to affect genetic inheritance, including individual disease risk, and even human evolution, the authors say. The study indicates, in fact, that people with different timing programs have different patterns of replication error, which affects mutation risk, across their genomes. McCarroll’s team, for example, found that differences in replication timing could explain why some people are more prone than others to certain blood cancers.
“I think this is the first time we can pinpoint genetic influences on replication timing in any organism,” says Koren.
Studies that uncover the variations in DNA replication timing—and the potential effects on mutation risk for disease—could flourish now that the team has shown that “all you need to do to study replication timing is grow cells and sequence their DNA, which everyone is doing these days,” says Koren. The fast, efficient method could, he adds, “transform the field because we can now do experiments in large scale.”
“We found that there is biological information in genome sequence data,” adds McCarroll. “But this was still an accidental biological experiment. Now imagine the results when we and others actually design experiments to study this phenomenon.”
Image: Dr. Torsten Wittmann/Science Source